As highlighted by the RDoC Negative Valence Systems Domain workshop, attentional biases to affective cues play a key role in the constructs of Responses to sustained threat and Loss. The neural circuitry underlying attentional biases relevant to both constructs is relatively well understood and is driven by a combination of bottom-up (amygdala) and top-down (regions of prefrontal cortex) processes. Despite their common neural influences, attentional biases relevant to threat versus loss are hypothesized to differ in their focus and time course. For example, responses to sustained threat are thought to be characterized by quicker initial allocation of attention toward threatening stimuli (e.g., angry faces). In contrast, responses to loss are thought to be characterized by deficits in the ability t disengage attention from sad faces. These attentional biases are hypothesized to develop during childhood, stabilize in adolescence, and contribute to the development and maintenance of psychopathology across the lifespan. Although there is growing support for these theories among adults and children, there are also a number of mixed findings in the literature, which we believe have resulted from the inadequate assessment of this key construct. To achieve the RDoC goal of developing new ways of classifying disorders based on dimensions of observable behaviors and brain functions, we need a more detailed understanding of which specific components of attention are disrupted in response to sustained threat and loss. This study will include 1,000 children aged 7-11 years and their mothers. Primary Aim 1 is to conduct a fine-grained examination of children's attentional biases using both behavioral (eyetracking) and physiological (event-related potential; ERP) indices to determine which specific components of children's attention are biased in relation to their broad symptoms of depression and anxiety, as well as the more specific symptom domains of low positive affect and physiological hyperarousal. Primary Aim 2 is to provide a better understanding of the genetic and epigenetic influences on these biases. We will utilize a circuit-level approach to examine aggregate levels of influence among genes known to be differentially expressed in amygdala versus PFC in this age group. Building from models of differential susceptibility to environmental influence, we will also examine how these genetic and epigenetic influences operate within the context of specific environmental influences. Finally, given that many maternal influences on children's attentional biases likely confound environmental and genetic factors, Primary Aim 3 is to examine attentional plasticity in the context of a laboratory-based conditioning task. We will examine genetic and epigenetic influences on changes in children's attentional biases as well as the generalizability of conditioning effects to a novel assessment of attentional allocation. Our goal is that this research will lead to a more detailed understanding of psychopathology in youth, emphasizing a new way of categorizing psychology based on the neural circuits disrupted, which is manifest as biased processing of emotional cues in ones environment. PUBLIC HEALTH RELEVANCE: The proposed project represents an important step in understanding a key construct within the RDoC Negative Valence Systems - attentional biases for emotional cues. It will provide detailed information regarding the behavioral, psychophysiological, genetic, epigenetic, and environmental foundations of these biases. As such, it will help pave the way for better characterizing internalizing psychopathology in youth, and provide the groundwork for more focused interventions.